Randomized trial of anakinra plus zinc vs. prednisone for severe alcohol-associated hepatitis.

BACKGROUND & AIMS: Severe alcohol-associated hepatitis (SAH) is associated with high 90-day mortality. Glucocorticoid therapy for 28 days improves 30- but not 90-day survival. We assessed the efficacy and safety of a combination of anakinra, an IL-1 antagonist, plus zinc (A+Z) compared to prednisone using the Day-7 Lille score as a stopping rule in patients with SAH. METHODS: In this phase IIb double-blind randomized trial in adults with SAH and MELD scores of 20-35, participants were randomized to receive either daily anakinra 100 mg subcutaneously for 14 days plus daily zinc sulfate 220 mg orally for 90 days, or daily prednisone 40 mg orally for 30 days. Prednisone or prednisone placebo was stopped if Day-7 Lille score was >0.45. All study drugs were stopped for uncontrolled infection or ≥5 point increase in MELD score. The primary endpoint was overall survival at 90 days. RESULTS: Seventy-three participants were randomized to prednisone and 74 to A+Z. The trial was stopped early after a prespecified interim analysis showed prednisone was associated with higher 90-day overall survival (90% vs. 70%; hazard ratio for death = 0.34, 95% CI 0.14-0.83, p = 0.018) and transplant-free survival (88% vs. 64%; hazard ratio for transplant or death = 0.30, 95% CI 0.13-0.69, p = 0.004) than A+Z. Acute kidney injury was more frequent with A+Z (45%) than prednisone (22%) (p = 0.001), but rates of infection were similar (31% in A+Z vs. 27% in prednisone, p = 0.389). CONCLUSIONS: Participants with SAH treated with prednisone using the Day-7 Lille score as a stopping rule had significantly higher overall and transplant-free 90-day survival and lower incidence of acute kidney injury than those treated with A+Z. IMPACT AND IMPLICATIONS: There is no approved treatment for severe alcohol-associated hepatitis (SAH). In this double-blind randomized trial, patients with SAH treated with prednisone using the Lille stopping rule on Day 7 had higher 90-day overall and transplant-free survival and lower rates of acute kidney injury compared to patients treated with a combination of anakinra and zinc. The data support continued use of glucocorticoids for patients with SAH, with treatment discontinuation for those with a Lille score >0.45 on Day 7. TRIAL REGISTRATION: NCT04072822.

Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease.

BACKGROUND: Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease. METHODS: We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed. RESULTS: A total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2±4.2 ml per minute per 1.73 m2 of body-surface area and the mean number of antihypertensive medications prescribed was 3.4±1.4. At randomization, the mean 24-hour ambulatory systolic blood pressure was 142.6±8.1 mm Hg in the chlorthalidone group and 140.1±8.1 mm Hg in the placebo group and the mean 24-hour ambulatory diastolic blood pressure was 74.6±10.1 mm Hg and 72.8±9.3 mm Hg, respectively. The adjusted change in 24-hour systolic blood pressure from baseline to 12 weeks was -11.0 mm Hg (95% confidence interval [CI], -13.9 to -8.1) in the chlorthalidone group and -0.5 mm Hg (95% CI, -3.5 to 2.5) in the placebo group. The between-group difference was -10.5 mm Hg (95% CI, -14.6 to -6.4) (P<0.001). The percent change in the urinary albumin-to-creatinine ratio from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50 percentage points (95% CI, 37 to 60). Hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group. CONCLUSIONS: Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).

Impact of Finerenone-Induced Albuminuria Reduction on Chronic Kidney Disease Outcomes in Type 2 Diabetes : A Mediation Analysis.

BACKGROUND: In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces cardiovascular and kidney failure outcomes. Finerenone also lowers the urine albumin-to-creatinine ratio (UACR). Whether finerenone-induced change in UACR mediates cardiovascular and kidney failure outcomes is unknown. OBJECTIVE: To quantify the proportion of kidney and cardiovascular risk reductions seen over a 4-year period mediated by a change in kidney injury, as measured by the change in log UACR between baseline and month 4. DESIGN: Post hoc mediation analysis using pooled data from 2 phase 3, double-blind trials of finerenone. (ClinicalTrials.gov: NCT02540993 and NCT02545049). SETTING: Several clinical sites in 48 countries. PATIENTS: 12 512 patients with CKD and T2D. INTERVENTION: Finerenone and placebo (1:1). MEASUREMENTS: Separate mediation analyses were done for the composite kidney (kidney failure, sustained ≥57% decrease in estimated glomerular filtration rate from baseline [approximately a doubling of serum creatinine], or kidney disease death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) outcomes. RESULTS: At baseline, median UACR was 514 mg/g. A 30% or greater reduction in UACR was seen in 3338 (53.2%) patients in the finerenone group and 1684 (27.0%) patients in the placebo group. Reduction in UACR (analyzed as a continuous variable) mediated 84% and 37% of the treatment effect on the kidney and cardiovascular outcomes, respectively. When change in UACR was analyzed as a binary variable (that is, whether the guideline-recommended 30% reduction threshold was met), the proportions mediated for each outcome were 64% and 26%, respectively. LIMITATION: The current findings are not readily extendable to other drugs. CONCLUSION: In patients with CKD and T2D, early albuminuria reduction accounted for a large proportion of the treatment effect against CKD progression and a modest proportion of the effect against cardiovascular outcomes. PRIMARY FUNDING SOURCE: Bayer AG.

A flexible time-varying coefficient rate model for panel count data.

Panel count regression is often required in recurrent event studies, where the interest is to model the event rate. Existing rate models are unable to handle time-varying covariate effects due to theoretical and computational difficulties. Mean models provide a viable alternative but are subject to the constraints of the monotonicity assumption, which tends to be violated when covariates fluctuate over time. In this paper, we present a new semiparametric rate model for panel count data along with related theoretical results. For model fitting, we present an efficient EM algorithm with three different methods for variance estimation. The algorithm allows us to sidestep the challenges of numerical integration and difficulties with the iterative convex minorant algorithm. We showed that the estimators are consistent and asymptotically normally distributed. Simulation studies confirmed an excellent finite sample performance. To illustrate, we analyzed data from a real clinical study of behavioral risk factors for sexually transmitted infections.

SARS-CoV-2 Infection, Hospitalization, and Death in Vaccinated and Infected Individuals by Age Groups in Indiana, 2021‒2022.

Objectives. To assess the effectiveness of vaccine-induced immunity against new infections, all-cause emergency department (ED) and hospital visits, and mortality in Indiana. Methods. Combining statewide testing and immunization data with patient medical records, we matched individuals who received at least 1 dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines with individuals with previous SARS-CoV-2 infection on index date, age, gender, race/ethnicity, zip code, and clinical diagnoses. We compared the cumulative incidence of infection, all-cause ED visits, hospitalizations, and mortality. Results. We matched 267 847 pairs of individuals. Six months after the index date, the incidence of SARS-CoV-2 infection was significantly higher in vaccine recipients (6.7%) than the previously infected (2.9%). All-cause mortality in the vaccinated, however, was 37% lower than that of the previously infected. The rates of all-cause ED visits and hospitalizations were 24% and 37% lower in the vaccinated than in the previously infected. Conclusions. The significantly lower rates of all-cause ED visits, hospitalizations, and mortality in the vaccinated highlight the real-world benefits of vaccination. The data raise questions about the wisdom of reliance on natural immunity when safe and effective vaccines are available. (Am J Public Health. 2023;113(1):96-104. https://doi.org/10.2105/AJPH.2022.307112).

The influence of social and environmental determinants of health on hospitalizations for pediatric asthma.

BACKGROUND: Asthma is the most common chronic disease of childhood, and has several social, environmental, and demographic factors potentially influential to its disease burden. This study sought to determine the influence of these factors on hospital admissions and readmissions for pediatric asthma. METHODS: This was a retrospective cohort study using data from the Indiana Network for Patient Care, a state-wide health information exchange in the United States. Study participants were children 2-18 years old admitted to the hospital with a respiratory diagnostic code between 2010 and 2021. Clinical variables were obtained from electronic health record data, and social and environmental determinants of health data were obtained from the Indiana Social Assets and Vulnerabilities Indicators using geocoding systems. Negative binomial models were used to examine community level social and environmental risk factors modifying the relationship between patient characteristics and the risk of asthma-related hospitalizations and 30-day readmissions. RESULTS: The study sample included 25,063 patients with an average follow-up of 9 (SD = 5) years. Of these, there were 17,816 asthma-related admissions. There were a total of 1,037 asthma-related 30-day readmissions, with an incidence rate of readmissions relative to total visits of 0.028 per person-year. A high social vulnerability index (SVI) was associated with an increased rate of hospital admissions (Proportion attributable ratio: 1.09, 95%CI (1.03,1.15), p < 0.05). No environmental determinants of health were significantly associated with hospitalization rate. CONCLUSION: High SVI was significantly associated with increased risk of total hospital admissions for pediatric asthma.

Using Palliative Leaders in Facilities to Transform Care for People with Alzheimer's Disease (UPLIFT-AD): protocol of a palliative care clinical trial in nursing homes.

BACKGROUND: Palliative care is an effective model of care focused on maximizing quality of life and relieving the suffering of people with serious illnesses, including dementia. Evidence shows that many people receiving care in nursing homes are eligible for and would benefit from palliative care services. Yet, palliative care is not consistently available in nursing home settings. There is a need to test pragmatic strategies to implement palliative care programs in nursing homes. METHODS/DESIGN: The UPLIFT-AD (Utilizing Palliative Leaders in Facilities to Transform care for people with Alzheimer's Disease) study is a pragmatic stepped wedge trial in 16 nursing homes in Maryland and Indiana, testing the effectiveness of the intervention while assessing its implementation. The proposed intervention is a palliative care program, including 1) training at least two facility staff as Palliative Care Leads, 2) training for all staff in general principles of palliative care, 3) structured screening for palliative care needs, and 4) on-site specialty palliative care consultations for a one-year intervention period. All residents with at least moderate cognitive impairment, present in the facility for at least 30 days, and not on hospice at baseline are considered eligible. Opt-out consent is obtained from legal decision-makers. Outcome assessments measuring symptoms and quality of care are obtained from staff and family proxy respondents at four time points: pre-implementation (baseline), six months after implementation, at 12 months (conclusion of implementation), and six months after the end of implementation. Palliative care attitudes and practices are assessed through surveys of frontline nursing home staff both pre- and post-implementation. Qualitative and quantitative implementation data, including fidelity assessments and interviews with Palliative Care Leads, are also collected. The study will follow the Declaration of Helsinki. DISCUSSION: This trial assesses the implementation and effectiveness of a robust palliative care intervention for residents with moderate-to-advanced cognitive impairment in 16 diverse nursing homes. The intervention represents an innovative, pragmatic approach that includes both internal capacity-building of frontline nursing home staff, and support from external palliative care specialty consultants. TRIAL REGISTRATION: The project is registered on ClinicalTrials.gov: NCT04520698.

Population-based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer's disease in African Americans.

INTRODUCTION: African Americans (AAs) and European Americans (EAs) differ in Alzheimer's disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials. METHODS: We conducted race-conscious pharmacoepidemiologic studies of 5.62 million older individuals (age ≥60) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan-Meier analysis, and log-rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan's target and AD. RESULTS: We identified that moderate/high telmisartan exposure was significantly associated with a reduced incidence of AD in the AAs compared to low/no telmisartan exposure (hazard ratio [HR] = 0.77, 95% CI: 0.65-0.91, p-value = 0.0022), but not in the non-Hispanic EAs (HR = 0.97, 95% CI: 0.89-1.05, p-value = 0.4110). Sensitivity and sex-/age-stratified patient subgroup analyses identified that telmisartan's medication possession ratio (MPR) and average hypertension daily dosage were significantly associated with a stronger reduction in the incidence of both AD and dementia in AAs. Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA-specific beneficial effects of telmisartan for AD. DISCUSSION: Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD. HIGHLIGHTS: Telmisartan is associated with lower risk of Alzheimer's disease (AD) in African Americans (AAs). Telmisartan is the only angiotensin II receptor blockers having PPAR-γ agonistic properties with beneficial anti-diabetic and renal function effects, which mitigate AD risk in AAs. Mendelian randomization (MR) analysis demonstrates the specificity of telmisartan's protective mechanism to AAs.

NIH Funding, Research Productivity, and Scientific Impact: a 20-Year Study.

BACKGROUND: The Research Project Grant (R01) is the oldest grant mechanism used by the National Institutes of Health (NIH). Receiving an R01 award is often taken as a sign of scientific success. We presented normative data on multiple productivity and impact metrics for a more objective assessment of funded grants' scientific success. METHODS: All initial R01 grants awarded by NIH in the year 2000 were prospectively followed and evaluated using the numbers of publications and citations, as well as the h-indices at the grant level. We examined the variability, time trends, and relations among these metrics to better understand the funded projects' cumulative output and impact. RESULTS: In the 20 years since initial funding, 4451 R01 grants generated a total of 55,053 publications. These publications were cumulatively cited 3,705,553 times over 736,811 citation years. The median number of publications was 8 (25th, 75th percentiles 4, 17) per grant for the entire 20-year duration. The median number of citations and the median h-index were 441 (25th, 75th percentiles 156, 1061) and 7 (25th, 75th percentiles 4, 13) per grant, respectively. The time courses of publication, citation, and accumulation of h-index were highly variable among the awarded grants. Although the metrics were correlated within an award, they reflected the grant's success in different domains. CONCLUSION: Numbers of publications, citations, and h-indices vary greatly among funded R01 grants. When used together, these metrics provide a more complete picture of the productivity and long-term impact of a funded grant.

Ten year trends in hospital encounters for pediatric asthma: an Indiana experience.

INTRODUCTION: Pediatric asthma is a common cause of emergency department visits, hospital admissions, and mortality. Population incidence studies have historically used large-scale survey data. We measured these epidemiologic trends using a health information exchange. METHODS: In this retrospective cohort study, we used electronic health record data from a regional health information exchange to study clinical trends in pediatric patients presenting to the hospital for asthma in the State of Indiana. Data was obtained from 2010 to 2019 and included all patients ages 2-18 years. Study participants were identified using international classification of disease codes. The measured outcomes were number of hospital encounters per year, percentage of admissions per year, and mortality rates. RESULTS: Data included 50,393 unique patients and 88,772 unique encounters, with 57% male patients. Over the ten-year period, hospital encounters ranged from 5000 to 8000 per year with no change in trajectory. Between 2010 and 2012, the percent of encounters admitted to the hospital was ∼30%. This decreased to ∼20-25% for 2015-2019. Patient mortality rates increased from 1 to 3 per 1000 patient encounters in 2010-2014 to between 5 and 7 per 1000 patient encounters from 2016 to 2019. White patients had a significantly higher admission percentage compared to other racial groups, but no difference in mortality rate. CONCLUSIONS: Asthma continues to be a common condition requiring hospital care for pediatric patients. Regional health information exchanges can enable public health researchers to follow asthma trends in near real time, and have potential for informing patient-level public health interventions.

Age-specific rates of hospital transfers in long-stay nursing home residents.

INTRODUCTION: hospital transfers and admissions are critical events in the care of nursing home residents. We sought to determine hospital transfer rates at different ages. METHODS: a cohort of 1,187 long-stay nursing home residents who had participated in a Centers for Medicare and Medicaid demonstration project. We analysed the number of hospital transfers of the study participants recorded by the Minimum Data Set. Using a modern regression technique, we depicted the annual rate of hospital transfers as a smooth function of age. RESULTS: transfer rates declined with age in a nonlinear fashion. Rates were the highest among residents younger than 60 years of age (1.30-2.15 transfers per year), relatively stable between 60 and 80 (1.17-1.30 transfers per year) and lower in those older than 80 (0.77-1.17 transfers per year). Factors associated with increased risk of transfers included prior diagnoses of hip fracture (annual incidence rate ratio or IRR: 2.057, 95% confidence interval (CI): [1.240, 3.412]), dialysis (IRR: 1.717, 95% CI: [1.313, 2.246]), urinary tract infection (IRR: 1.755, 95% CI: [1.361, 2.264]), pneumonia (IRR: 1.501, 95% CI: [1.072, 2.104]), daily pain (IRR: 1.297, 95% CI: [1.055,1.594]), anaemia (IRR: 1.229, 95% CI [1.068, 1.414]) and chronic obstructive pulmonary disease (IRR: 1.168, 95% CI: [1.010,1.352]). Transfer rates were lower in residents who had orders reflecting preferences for comfort care (IRR: 0.79, 95% CI: [0.665, 0.936]). DISCUSSION: younger nursing home residents may require specialised interventions to reduce hospital transfers; declining transfer rates with the oldest age groups may reflect preferences for comfort-focused care.

The design and conduct of a pragmatic cluster randomized trial of an advance care planning program for nursing home residents with dementia.

BACKGROUND/AIMS: A significant number of people with Alzheimer's disease or related dementia diagnoses will be cared for in nursing homes near the end of life. Advance care planning (ACP), the process of eliciting and documenting patient-centered preferences for care, is considered essential to providing high quality care for this population. Nursing homes are currently required by regulations to offer ACP to residents and families, but no training requirements exist for nursing home staff, and approaches to fulfilling this regulatory and ethical responsibility vary. As a result, residents may receive care inconsistent with their goals, such as unwanted hospitalizations. Pragmatic trials offer a way to develop and test ACP in real-world settings to increase the likelihood of adoption of sustainable best practices. METHODS: The "Aligning Patient Preferences-a Role Offering Alzheimer's patients, Caregivers, and Healthcare Providers Education and Support (APPROACHES)" project is designed to pragmatically test and evaluate a staff-led program in 137 nursing homes (68 = intervention, 69 = control) owned by two nursing home corporations. Existing nursing home staff receive standardized training and implement the ACP Specialist program under the supervision of a corporate lead. The primary trial outcome is the annual rate of hospital transfers (admissions and emergency department visits). Consistent with the spirit of a pragmatic trial, study outcomes rely on data already collected for quality improvement, clinical, or billing purposes. Configurational analysis will also be performed to identify conditions associated with implementation. RESULTS: Partnerships with large corporate companies enable the APPROACHES trial to rely on corporate infrastructure to roll out the intervention, with support for a corporate implementation lead who is charged with the initial introduction and ongoing support for nursing home-based ACP Specialists. These internal champions connect the project with other company priorities and use strategies familiar to nursing home leaders for the initiation of other programs. Standardized data collection across nursing homes also supports the conduct of pragmatic trials in this setting. DISCUSSION: Many interventions to improve care in nursing homes have failed to demonstrate an impact or, if successful, maintain an impact over time. Pragmatic trials, designed to test interventions in real-world contexts that are evaluated through existing data sources collected routinely as part of clinical care, are well suited for the nursing home environment. A robust program that increases access to ACP for nursing home residents has the potential to increase goal-concordant care and is expected to reduce hospital transfers. If successful, the ACP Specialist Program will be primed for rapid translation into nursing home practice to reduce unwanted, burdensome hospitalizations and improve the quality of care for residents with dementia.

Aldosterone sensitivity: an opportunity to explore the pathogenesis of hypertension.

Aldosterone sensitivity is defined as an outcome variable for a given circulating level of aldosterone. In basic and translational studies, aldosterone sensitivity has been measured in differential tissue responses, e.g., lower urine sodium and higher urine potassium, as an index of the renal response; in clinical studies, aldosterone sensitivity has been measured in differential blood pressure responses. The concept of aldosterone sensitivity disrupts the conventional wisdom of the renin-angiotensin-aldosterone system and has the potential to uncover novel mechanisms of hypertension. Here, we review basic and translational science studies that uncovered differential renal responses to aldosterone and connect this earlier work to more recent observational studies and randomized trials that have demonstrated differential blood pressure responses for a given level of aldosterone in healthy and hypertensive persons. Black race and older age are associated with higher aldosterone sensitivity and blood pressure. We also discuss gaps in the field and how future basic and clinical studies might inform mechanisms of differential sensitivity.

A Contextual Approach to the Psychological Study of Identity Concealment: Examining Direct, Interactive, and Indirect Effects of Structural Stigma on Concealment Motivation Across Proximal and Distal Geographic Levels.

Psychological theories of identity concealment locate the ultimate source of concealment decisions within the social environment, yet most studies have not explicitly assessed stigmatizing environments beyond the immediate situation. We advanced the identity-concealment literature by objectively measuring structural forms of stigma related to sexual orientation (e.g., social policies) at proximal and distal geographic levels. We linked these measures to a new, population-based data set of 502 gay and bisexual men (residing in 44 states and Washington, DC; 269 counties; and 354 cities) who completed survey items about stigma, including identity-concealment motivation. Among gay men, the association between structural stigma and concealment motivation was (a) observed across three levels (city, county, and state), (b) conditional on one's exposure at another geographic level (participants reported the least motivations to conceal their identity if they resided in both cities and states that were lowest in structural stigma), and (c) mediated by subjective perceptions of greater structural stigma.

Robust estimation of heterogeneous treatment effects using electronic health record data.

Estimation of heterogeneous treatment effects is an essential component of precision medicine. Model and algorithm-based methods have been developed within the causal inference framework to achieve valid estimation and inference. Existing methods such as the A-learner, R-learner, modified covariates method (with and without efficiency augmentation), inverse propensity score weighting, and augmented inverse propensity score weighting have been proposed mostly under the square error loss function. The performance of these methods in the presence of data irregularity and high dimensionality, such as that encountered in electronic health record (EHR) data analysis, has been less studied. In this research, we describe a general formulation that unifies many of the existing learners through a common score function. The new formulation allows the incorporation of least absolute deviation (LAD) regression and dimension reduction techniques to counter the challenges in EHR data analysis. We show that under a set of mild regularity conditions, the resultant estimator has an asymptotic normal distribution. Within this framework, we proposed two specific estimators for EHR analysis based on weighted LAD with penalties for sparsity and smoothness simultaneously. Our simulation studies show that the proposed methods are more robust to outliers under various circumstances. We use these methods to assess the blood pressure-lowering effects of two commonly used antihypertensive therapies.

Facility and resident characteristics associated with variation in nursing home transfers: evidence from the OPTIMISTIC demonstration project.

BACKGROUND: Centers for Medicare and Medicaid Services (CMS) funded demonstration project to evaluate financial incentives for nursing facilities providing care for 6 clinical conditions to reduce potentially avoidable hospitalizations (PAHs). The Optimizing Patient Transfers, Impacting Medical Quality, and Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) site tested payment incentives alone and in combination with the successful nurse-led OPTIMISTIC clinical model. Our objective was to identify facility and resident characteristics associated with transfers, including financial incentives with or without the clinical model. METHODS: This was a longitudinal analysis from April 2017 to June 2018 of transfers among nursing home residents in 40 nursing facilities, 17 had the full clinical + payment model (1726 residents) and 23 had payment only model (2142 residents). Using CMS claims data, the Minimum Data Set, and Nursing Home Compare, multilevel logit models estimated the likelihood of all-cause transfers and PAHs (based on CMS claims data and ICD-codes) associated with facility and resident characteristics. RESULTS: The clinical + payment model was associated with 4.1 percentage points (pps) lower risk of all-cause transfers (95% confidence interval [CI] - 6.2 to - 2.1). Characteristics associated with lower PAH risk included residents aged 95+ years (- 2.4 pps; 95% CI - 3.8 to - 1.1), Medicare-Medicaid dual-eligibility (- 2.5 pps; 95% CI - 3.3 to - 1.7), advanced and moderate cognitive impairment (- 3.3 pps; 95% CI - 4.4 to - 2.1; - 1.2 pps; 95% CI - 2.2 to - 0.2). Changes in Health, End-stage disease and Symptoms and Signs (CHESS) score above most stable (CHESS score 4) increased the risk of PAH by 7.3 pps (95% CI 1.5 to 13.1). CONCLUSIONS: Multiple resident and facility characteristics are associated with transfers. Facilities with the clinical + payment model demonstrated lower risk of all-cause transfers compared to those with payment only, but not for PAHs.

The point of diminishing returns in juvenile probation: Probation requirements and risk of technical probation violations among first-time probation-involved youth.

Technical probation violations are common among probation-involved youth, and across many jurisdictions, may result in detention or residential placement. The current study examined prevalence of technical violations occurring during one's first probation period, the average time to technical violation, and individual-level and justice-related factors related to technical violations among probation-involved youth in a juvenile justice system. We analyzed electronic criminal records of 18,289 probation-involved youth following their first arrest (68.7% male, 53.9% Black, Mage=15.2). Technical violation was defined as a violation resulting from a non-criminal incident. We examined effects of charge severity, probation conditions (e.g., electronic monitoring) and program referrals (e.g., mental health) on likelihood of technical violation utilizing survival analysis stratified by race. Across 18,289 youth, 15.3% received a technical violation during their first probation; Black youth violated more quickly compared to White youth (log-rank test p<.001). In multivariate survival analyses, the hazard for time to technical violation was higher for Black youth compared to white youth (p<.001), males (p=.04), and younger youth (p<.001). Youth assigned to more probation requirements violated more quickly. Electronic monitoring and education, mental health, and drug programs were associated with shorter time to violation, controlling for race, ethnicity, and charge severity. Black youth violate more quickly compared to White youth. Across all youth, assignment to more probation requirements increased risk of technical violation and shorter time to violation. Despite the benefit of probation interventions, system-level efforts are needed to help youth adhere to probation requirements and successfully complete probation.

Design and Baseline Characteristics of the Chlorthalidone in Chronic Kidney Disease (CLICK) Trial.

BACKGROUND: Hypertension often accompanies chronic kidney disease (CKD), and diuretics are widely prescribed to reduce blood pressure (BP). Chlorthalidone (CTD) is a thiazide-like diuretic and an effective antihypertensive drug, yet little data exist to support its use in treating hypertension in individuals with advanced CKD. METHODS: Chlorthalidone in Chronic Kidney Disease (CLICK) is a phase II, single-institution, multicenter, double-blind randomized control trial to test the hypothesis that CTD improves BP, through reduction of extracellular fluid volume, and results in target organ protection in patients with stage 4 CKD and poorly controlled hypertension. After a single-blind placebo run-in for 2 weeks and confirmation of hypertension by 24-h ambulatory blood pressure (ABP), patients are randomized to either placebo or CTD 12.5 mg once daily (QD) followed by dose escalation. Randomization is stratified by prior loop diuretic use, and the double-blind phase lasts 12 weeks. With a total of 160 patients, the study will have ≥80% power to detect a 6 mm Hg difference in systolic 24-h ABP between the 2 treatment groups. RESULTS: Between June 2016 and October 2019, 131 patients have been randomized. The baseline characteristics are as follows: average age 65.8 years, 79% men, 36% Black, 79% with diabetes, mean eGFR 23.2 mL/min/1.73 m2, median urine albumin/creatinine ratio 923 mg/g, average number of BP medications 3.4, 60% on loop diuretics, and 24-h ABP averaged 141.7/73.8 mm Hg. CONCLUSION: Among patients with stage 4 CKD and uncontrolled hypertension, CLICK should answer the question whether CTD is safe and effective.

Comparison of nonlinear curves and surfaces.

Estimation of nonlinear curves and surfaces has long been the focus of semiparametric and nonparametric regression analysis. What has been less studied is the comparison of nonlinear functions. In lower-dimensional situations, inference typically involves comparisons of curves and surfaces. The existing comparative procedures are subject to various limitations, and few computational tools have been made available for off-the-shelf use. To address these limitations, two modified testing procedures for nonlinear curve and surface comparisons are proposed. The proposed computational tools are implemented in an R package, with a syntax similar to that of the commonly used model fitting packages. An R Shiny application is provided with an interactive interface for analysts who do not use R. The new tests are consistent against fixed alternative hypotheses. Theoretical details are presented in an appendix. Operating characteristics of the proposed tests are assessed against the existing methods. Applications of the methods are illustrated through real data examples.